Sensor for transcutaneous measurement of vascular access blood flow

ABSTRACT

An optical sensor includes photoemitter and photodetector elements at multiple spacings (d 1 , d 2 ) for the purpose of measuring the bulk absorptivity (α) of an area immediately surrounding and including a hemodialysis access site, and the absorptivity (α o ) of the tissue itself. At least one photoemitter element and at least one photodetector element are provided, the total number of photoemitter and photodetector elements being at least three. The photoemitter and photodetector elements are collinear and alternatingly arranged, thereby allowing the direct transcutaneous determination of vascular access blood flow.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present patent application is a divisional of application Ser. No. 09/750,076, filed Dec. 29, 2000, are is incorporated herein by reference in its entirety.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to apparatus for non-invasively measuring one or more blood parameters. More specifically, the invention relates to apparatus for the transcutaneous measurement of vascular access blood flow. The invention can also be used for precise access location, as a “flow finder,” and also can be used to locate grafts and to localize veins in normal patients for more efficient canulatization.

2. Related Art

Routine determination of the rate of blood flow within the vascular access site during maintenance hemodialysis is currently considered an integral component of vascular access assessment. While the relative importance of vascular access flow rates and venous pressure measurements in detecting venous stenoses is still somewhat controversial, both the magnitude and the rate of decrease in vascular access flow rate have been previously shown to predict venous stenoses and access site failure. The traditional approach for determining the vascular access flow rate is by Doppler flow imaging; however, these procedures are expensive and cannot be performed during routine hemodialysis, and the results from this approach are dependent on the machine and operator.

Determination of the vascular access flow rate can also be accurately determined using indicator dilution methods. Early indicator dilution studies determined the vascular access flow rate by injecting cardiogreen or radiolabeled substances at a constant rate into the arterial end of the access site and calculated the vascular access flow rate from the steady state downstream concentration of the injected substance. These early attempts to use indicator dilution methods were limited to research applications since this approach could not be routinely performed during clinical hemodialysis. It has long been known that in order to determine the vascular access flow (ABF) rate during the hemodialysis procedure, the dialysis blood lines can be reversed (by switching the arterial and venous connections) to direct the blood flow within the hemodialysis circuit in order to facilitate the injection of an indicator in the arterial end of the access site and detect its concentration downstream (N. M. Krivitski, “Theory and validation of access flow measurements by dilution technique during hemodialysis,” Kidney Int 48:244-250, 1995; N. M. Krivitski, “Novel method to measure access flow during hemodialysis by ultrasound velocity dilution technique,” ASAIO J 41:M741-M745, 1995; and T. A. Depner and N. M. Krivitski, “Clinical measurement of blood flow in hemodialysis access fistulae and grafts by ultrasound dilution,” ASAIO J 41:M745-M749, 1995)). D. Yarar et al., Kidney Int., 65: 1129-1135 (1999), developed a similar method using change in hematocrit to determine ABF. Various modifications of this approach have been subsequently developed. While these latter indicator dilution methods permit determination of the vascular access flow rate during routine hemodialysis, reversal of the dialysis blood lines from their normal configuration is inconvenient and time-consuming since it requires that the dialyzer blood pump be stopped and the dialysis procedure is relatively inefficient during the evaluation of the flow rate which can take up to twenty minutes. Furthermore, some of these indicator dilution methods also require accurate determination of the blood flow rate.

Clinical usefulness and ease of use are major developmental criteria. From a routine clinical point of view the need to design a simple sensor, easily attached to the patient, requiring no line reversals, no knowledge of the dialysis blood flow rate, Q_(b), and transcutaneously applied to skin, thereby accomplishing the measurement within a total of 1-2 minutes, is crucial to have repeated, routine meaningful ABF trend information, whereby access health is easily tracked.

SUMMARY OF THE INVENTION

It is therefore an object of the present invention to provide apparatus for non-invasively measuring one or more blood parameters.

It is another object of the present invention to provide an optical hematocrit sensor that can detect changes in hematocrit transcutaneously.

It is still another object of the invention to provide an optical hematocrit sensor that can be used to determine the vascular access flow rate within 2 minutes and without reversal of the dialysis blood lines or knowledge of Q_(b), all transcutaneously.

These and other objects of the invention are achieved by the provision of an optical sensor including complementary emitter and detector elements at multiple spacings (d₁, d₂) for the purpose of measuring the bulk absorptivity (α) of the volume immediately surrounding and including the access site, and the absorptivity (α_(o)) of the tissue itself.

In one aspect of the invention, the optical sensor system comprises an LED of specific wavelength and a complementary photodetector. A wavelength of 805 nm-880 nm, which is near the known isobestic wavelength for hemoglobin, is used.

When the sensor is placed on the surface of the skin, the LED illuminates a volume of tissue, and a small fraction of the light absorbed and back-scattered by the media is detected by the photodetector. The illuminated volume as seen by the photodetector can be visualized as an isointensity ellipsoid, as individual photons of light are continuously scattered and absorbed by the media. Because a wavelength of 805 nm-880 nm is used, hemoglobin of the blood within the tissue volume is the principal absorbing substance. The scattering and absorbing characteristics are mathematically expressed in terms of a bulk attenuation coefficient (α) that is specific to the illuminated media. The amount of light detected by the photodetector is proportional via a modified Beer's law formula to the instantaneous net α value of the media.

When the volume of tissue illuminated includes all or even part of the access, the resultant α value includes information about both the surrounding tissue and the access itself. In order to resolve the signal due to blood flowing within the access from that due to the surrounding tissues, the sensor system illuminates adjacent tissue regions on either side of the access. Values of α_(o) for tissue regions not containing the access are then used to normalize the signal, thus providing a baseline from which relative changes in access hematocrit can be assessed.

Other objects, features and advantages of the present invention will be apparent to those skilled in the art upon a reading of this specification including the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is better understood by reading the following Detailed Description of the Preferred Embodiments with reference to the accompanying drawing figures, in which like reference numerals refer to like elements throughout, and in which:

FIG. 1 is a diagrammatic view of a dialysis circuit in which a TQ_(a) hematocrit sensor in accordance with the present invention is placed at the hemodialysis vascular access site.

FIG. 2 is a perspective view of a first embodiment of a TQ_(a) hematocrit sensor in accordance with the present invention.

FIG. 3 is a bottom plan view of the TQ_(a) hematocrit sensor of FIG. 2.

FIG. 4 is a side elevational view of the TQ_(a) hematocrit sensor of FIG. 2.

FIG. 5 is a top plan view of the TQ_(a) hematocrit sensor of FIG. 2.

FIG. 6 is a cross-sectional view taken along line 6—6 of FIG. 2.

FIG. 7 is a diagrammatic view illustrating the TQ_(a) sensor of FIG. 2 and the illuminated volumes or “glowballs” produced by the emitters and seen by the detectors thereof.

FIG. 8 is a perspective view of a second embodiment of a TQ_(a) hematocrit sensor in accordance with the present invention.

FIG. 9 is a bottom plan view of the TQ_(a) hematocrit sensor of FIG. 8.

FIG. 10 is a side elevational view of the TQ_(a) hematocrit sensor of FIG. 8.

FIG. 11 is a top plan view of the TQ_(a) hematocrit sensor of FIG. 8.

FIG. 12 is a cross-sectional view taken along line 12—12 of FIG. 9.

FIG. 13 is a diagrammatic view illustrating the TQ_(a) hematocrit sensor of FIG. 8 and the illuminated volumes or “glowballs” produced by the emitters and seen by the detector thereof.

FIG. 14 is a perspective view of a third embodiment of a TQ_(a) hematocrit sensor in accordance with the present invention.

FIG. 15 is a bottom plan view of the TQ_(a) hematocrit sensor of FIG. 14.

FIG. 16 is a side elevational view of the TQ_(a) hematocrit sensor of FIG. 14.

FIG. 17 is a top plan view of the TQ_(a) hematocrit sensor of FIG. 14.

FIG. 18 is a cross-sectional view taken along line 18—18 of FIG. 15.

FIG. 19 is a diagrammatic view illustrating the TQ_(a) hematocrit sensor of FIG. 14 and the illuminated volumes or “glowballs” produced by the emitter and seen by the detectors thereof.

FIG. 20 is a perspective view of a fourth embodiment of a TQ_(a) hematocrit sensor in accordance with the present invention.

FIG. 21 is a partial cross-sectional view of the TQ_(a) hematocrit sensor of FIG. 20.

FIG. 22 is a diagrammatic view of the TQ_(a) hematocrit sensor of FIG. 20 showing the placement of the emitters and detectors relative to the access site.

FIGS. 23-26 are diagrammatic views illustrating the TQ_(a) hematocrit sensor of FIG. 20 and the illuminated volumes or “glowballs” produced by the emitters and seen by the detectors thereof.

FIG. 27 is a perspective view of a fifth embodiment of a TQ_(a) hematocrit sensor in accordance with the present invention.

FIG. 28 is a partial cross-sectional view of the TQ_(a) hematocrit sensor of FIG. 27.

FIG. 29 is a diagrammatic view of the TQ_(a) hematocrit sensor of FIG. 27 showing the placement of the emitters and detectors relative to the access site.

FIGS. 30-33 are diagrammatic views illustrating the TQ_(a) hematocrit sensor of FIG. 27 and the illuminated volumes or “glowballs” produced by the emitters and seen by the detectors thereof.

FIG. 34 is a cross-sectional view of a TQ_(a) hematocrit sensor in accordance with the present invention in the form of a disposable adhesive patch.

FIG. 35 is a graphical representation of a signal proportional to the hematocrit in the vascular access as recorded by a sensor and associated monitoring system in accordance with the invention.

FIG. 36 is a graphical representation of plotted values of the vascular access flow rate determined using a TQ_(a) sensor in accordance with the present invention versus that determined by a conventional HD₀₁ monitor.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

In describing preferred embodiments of the present invention illustrated in the drawings, specific terminology is employed for the sake of clarity. However, the invention is not intended to be limited to the specific terminology so selected, and it is to be understood that each specific element includes all technical equivalents that operate in a similar manner to accomplish a similar purpose.

The following abbreviations and variables are used throughout the present disclosure in connection with the present invention:

-   -   α=access site optical attenuation coefficient     -   α_(o)=non-access site optical attenuation coefficient     -   B_(o)=composite of all the non-access region S, K coefficients     -   C=proportionality scalar     -   CPR=cardiopulmonary recirculation     -   d=distance between the emitter and the detector     -   H=hematocrit, generally     -   H_(a)=hematocrit within the vascular access site     -   H_(ao)=hematocrit beneath the sensor (outside the dialyzer)     -   ΔH=change in hematocrit (H_(a)−H_(ao))     -   i=intensity of light, generally     -   I_(baseline)=baseline intensity (taken in the absence of a         bolus)     -   I_(measure)=light back-scattered from a turbid tissue sample     -   I_(o)=emitter radiation intensity     -   K=bulk absorption coefficient     -   K_(b)=access site blood coefficient     -   Q_(a)=vascular access blood flow rate     -   Q_(b)=dialyzer blood flow rate     -   Q_(f)=dialyzer ultrafiltration rate     -   Q_(i)=average injection inflow rate     -   S=bulk scattering coefficient     -   SD=standard deviation     -   SNR=signal-to-noise ratio     -   t=time (measured from time of injection)     -   TQ_(a)=transcutaneous access blood flow     -   V=known volume of saline injected into dialysis venous line     -   X_(b)=percentage of the access volume to the total volume         illuminated (access blood proration value)     -   X_(o)=percentage of the non-access area to the total volume

The optical hematocrit sensor in accordance with the present invention comprises a light emitting source (emitter) (preferably an LED of specific wavelength) and a complementary photodetector that can be placed directly on the skin over a vascular access site. The LED preferably emits light at a wavelength of 805 nm-880 nm, because it is near the known isobestic wavelength for hemoglobin, is commercially available, and has been shown to be effective in the optical determination of whole blood parameters such as hematocrit and oxygen saturation.

When the sensor is placed on the surface of the skin, the LED illuminates a volume of tissue, and a small fraction of the light absorbed and back-scattered by the media is detected by the photodetector. While light travels in a straight line, the illuminated volume as seen by the photodetector can be visualized as an isointensity ellipsoid, as individual photons of light are continuously scattered and absorbed by the media. Because a wavelength of 805 nm-880 nm is used, hemoglobin of the blood within the tissue volume is the principal absorbing substance. The scattering and absorbing characteristics are mathematically expressed in terms of a bulk attenuation coefficient (α) that is specific to the illuminated media. The amount of light detected by the photodetector is proportional via a modified Beer's law formula to the instantaneous net α value of the media.

When the volume of tissue illuminated includes all or even part of the access, the resultant α value includes information about both the surrounding tissue and the access itself. In order to resolve the signal due to blood flowing within the access from that due to the surrounding tissues, the sensor system illuminates adjacent tissue regions on either side of the access. Values of α_(o) for tissue regions not containing the access are then used to normalize the signal, thus providing a baseline from which relative changes can be assessed in access hematocrit in the access blood flowing directly under the skin.

FIG. 1 illustrates a dialysis circuit in which a TQ_(a) hematocrit sensor 12 in accordance with the present invention is placed over the hemodialysis vascular access site 14, with the dialysis arterial and venous blood lines 16 a and 16 b in the normal configuration, for measuring TQ_(a). A dialyzer 20 downstream of the vascular access site 14 and a syringe 22 for injecting a reference diluent (for example, saline) downstream of the dialyzer 20 are indicated. The hematocrits and flow rates under steady state conditions are also indicated, where Q_(a) is the access flow rate, Q_(b) is the dialyzer blood flow rate, Q_(i) is the injection flow rate, H_(a) is the hematocrit in the access flow, and H_(o) is the hematocrit at the sensor 12. The hematocrit sensor 12 is placed directly on the skin over the vascular access site 14 downstream of the venous dialysis needle 24.

As shown in FIG. 35, the sensor 12 and an associated monitoring system 30 records a signal proportional to the hematocrit in the vascular access site 14 (H_(a)). The monitoring system 30 can be a computer including a computer processor and memory, and output means such as a video monitor and printer (not shown). After a stable H_(a) value is obtained, a known volume (V) of normal saline is injected via the syringe 22 into the dialysis venous line 16 b, which reduces the hematocrit beneath the sensor 12 to a time-dependent hematocrit H_(o) during the injection.

Derivation of the equation used to calculate the vascular access flow rate when using the bolus injection indicator dilution approach is complex. However, the constant infusion and bolus injection indicator dilution approaches yield identical results; therefore, the governing equation was derived from steady state constant infusion principles. Consider the dialysis circuit in FIG. 1 where a steady infusion of saline occurs in the dialysis venous blood line 16 b (ultrafiltration at the dialyzer 20 is neglected). Red cell balance where the dialysis venous blood flow enters the access site 14 requires H _(a)(Q _(a) −Q _(b))+H _(a) Q _(b) =H _(o)(Q _(a) +Q _(i))  (1) Solving for Q_(a), the vascular access flow rate, yields $\begin{matrix} {Q_{a} = \frac{Q_{i}}{\frac{\Delta\quad H}{H_{o}}}} & (2) \end{matrix}$ where ΔH denotes H_(a)−H_(ao). This equation describes the changes in hematocrit at the sensor 12 during a constant infusion of normal saline in the dialysis venous blood line 16 b. (If ultrafiltration at the dialyzer 20 occurs at a rate of Q_(f), then the numerator in this equation becomes Q_(i)−Q_(f)).

Noting that Q_(i) is equivalent to the volume of saline injected in a specified time interval, equation (2) is therefore equivalent to: $\begin{matrix} {Q_{a} = \frac{V}{\int{{F\left( \frac{\Delta\quad H}{H} \right)}(t){\mathbb{d}t}}}} & (3) \end{matrix}$ to yield the vascular access flow rate (Q_(a)), where ΔH denotes H_(a)−H_(ao) and the integral (area under the curve) in the above equation is from the time of injection (t=0) to where the signal has returned to the baseline value (t=∞). This equation is valid independent of the rate of saline injection or the dialyzer blood flow rate. The signals detected by the TQ_(a) sensor 12 can be used to calculate ${F\left( \frac{\Delta\quad H}{H_{o}} \right)}.$ Determination ${fF}\left( \frac{\Delta\quad H}{H} \right)$

The percentage change in blood parameters (both macroscopic and microscopic) passing through the access site 14 may be measured in a variety of ways. Macroscopic parameters such as bulk density or flow energy can be measured by ultrasonic, temperature, or conductivity means. Microscopic parameters (sometimes called “physiologic or intrinsic” parameters) such as hematocrit or red cell oxygen content are measured by optical means. Each technique has its respective advantages and disadvantages, both rely on the quantity $\frac{\Delta\quad H}{H}.$ Inherent in all of these is the need to differentiate the access site 14, and parameter changes therein, from the surrounding tissue structure. The TQ_(a) sensor 12 in accordance with the present invention is positioned directly over the access site region 14 itself approximately 25 mm downstream of the venous needle 24, and is based upon optical back-scattering of monochromatic light (λ=805 nm-880 nm) from the blood flow in the access site 14 and the surrounding tissues. The theory on which the construction of the TQ_(a) sensor 12 is based requires the use of optical physics and laws associated with optical determination of physiologic elements including hematocrit.

Modified Beer's Law

Numerous studies have shown that light back-scattered from a turbid tissue sample follows a modified form of Beer's Law, I _(measured) =I _(o) Ae ^(−ad)  (4) where I_(o) is the radiation intensity emitted from the LED, A is a complex function of d and α of the various layers of tissue (epidermis, dermis, and subcutaneous tissue), d is the distance between the LED and detector, and α is the bulk optical attenuation coefficient. The α term is a function of the absorption and scattering nature of the tissue and has a strong dependence on hematocrit. $\begin{matrix} {\alpha \approx \frac{{- L}\quad n\quad\left( \frac{I_{measured}}{I_{o}} \right)}{d}} & (5) \end{matrix}$ Compartmentalization of α

A transcutaneously measured α value is actually a prorated composite measure of all the absorption and scattering elements contained within the illuminated volume or “glowball” of the emitter source, and typically includes the effects of tissue, water, bone, blood, and in the case of hemodialysis patients, the access site 14. In the determination of α, clearly only the blood flowing through the access site 14 is of interest. The task therefore becomes one of separating the effects of absorption and scattering of the access site 14 from that of surrounding tissue structure. Starting with the well known definition, α=√{square root over (3K(K+S))}  (6) where K is the bulk absorption coefficient and S is the bulk scattering coefficient, and separating the access site 14 from non-access blood coefficients and rearranging terms, X _(b) K _(b)≈α² −B _(o)  (7) where X_(b)=ratio of the access volume to the total volume illuminated

-   -   K_(b)=access blood coefficient     -   B_(o)=composite of all the non-access region S and K         coefficients         Now, letting the non-access components become α_(o) ²=B_(o), we         have         X _(b) K _(b) =α ²−α_(o) ²  (8)         In equation (6), the access blood coefficient, K_(b), is         directly proportional to hematocrit (H), K_(b)=H·C. Therefore,         X _(b) K _(b) =X _(b) ·H·C=α ²−α_(o) ²  (9)     -   where C is a proportionality scalar known from the literature or         empirically derived.

To determine α_(o), measurements are made in areas 130 b and 130 c near but not including the access site 14, as depicted, for example, in FIG. 7. If the tissue is more or less homogenous, it is only necessary to make a single reference α_(o) measurement, using either two emitters 202 a and 202 b and one detector 204 (as shown in FIG. 13) or one emitter 302 and two detectors 304 a and 304 b (as shown in FIG. 19), as discussed in greater detail hereinafter. On the other hand, if a gradient in α_(o) exists in the area of interest (and this is often the case in vivo) multiple measurements are made to establish the nature of the gradient and provide an averaged estimate of α_(o), using two emitters 102 a and 102 b and two detectors 104 a and 104 b, as discussed in greater detail hereinafter in connection with FIGS. 2-6.

Determination of $\frac{di}{i}$

The value of $\frac{di}{i}$ is defined as the time derivative of intensity i, normalized by i. This is expressed as $\begin{matrix} {{{\frac{di}{i} = {\frac{{X_{b} \cdot \Delta}\quad K_{b}}{\alpha}\left( {d - \frac{1}{\alpha}} \right)}},{{{where}\quad A} \approx \alpha},{{from}\quad{{equation}{\quad\quad}(4)}}}{{or},{{{X_{b} \cdot \Delta}\quad K_{b}} = \frac{\frac{d_{i}}{i}\alpha}{\left( {d - \frac{1}{\alpha}} \right)}}}} & (10) \end{matrix}$ wherein ΔK_(b) is proportional to ΔH. Hence, $\begin{matrix} {{{X_{b} \cdot \Delta}\quad{H \cdot C}} = {{{X_{b} \cdot \Delta}\quad K_{b}} = \frac{\frac{d_{i}}{i}\alpha}{\left( {d - \frac{1}{\alpha}} \right)}}} & (11) \end{matrix}$ To determine $\frac{d\quad i}{i},$ a baseline intensity (taken in the absence of a bolus) is first measured to establish a reference. The intensity is then measured as a time varying signal as the saline bolus is injected, I(t). The quantity $\frac{d\quad i}{i}$ is then calculated as $\begin{matrix} {\frac{d\quad i}{i} = \frac{I_{baseline} - {I(t)}}{I_{baseline}}} & (12) \end{matrix}$

Final Determination of $F\left( \frac{\Delta\quad H}{H} \right)$

The value $F\left( \frac{\Delta\quad H}{H} \right)$ is the ratio of equations (11) and (8), $\begin{matrix} {{F\left( \frac{\Delta\quad H}{H} \right)} = {\frac{\frac{d\quad i}{i}\alpha}{\left( {d - \frac{1}{\alpha}} \right)\left( {\alpha^{2} - \alpha_{o}^{2}} \right)}.}} & (13) \end{matrix}$ Since d is fixed and known $\frac{d\quad i}{i},$ α, and α_(o) are computed by equations (10) and (5). It is important to note that in the final ratio of ${F\left( \frac{\Delta\quad H}{H} \right)},$ the access blood proration value, X_(b), cancels out. This removes vascular access size, volume, or depth dependence from the final result. Likewise, the $\frac{d\quad i}{i}$ and $\frac{\alpha}{\alpha^{2} - \alpha_{o}^{2}}$ ratios eliminate skin color variations.

In order to use indicator dilution techniques to measure vascular access flow rates during routine hemodialysis, the indicator must be injected upstream and its concentration detected downstream in the blood flowing through the vascular access site 14. Reversing the dialysis blood lines 16 a and 16 b during the hemodialysis treatment permits application of indicator dilution by direct injection of the indicator into the dialysis venous tubing 16 b. Because the TQ_(a) sensor 12 can detect a dilution signal downstream of the venous needle 24 through the skin, a unique application of indicator dilution principles permits determination of the vascular access flow rate without reversal of the dialysis blood lines 16 a and 16 b. Various methods of measuring vascular access blood flow rate, as well as a method for locating accesses and grafts and localizing veins in normal patients, using the TQ_(a) sensor 12 are described in co-pending U.S. application Ser. No. 09/750,122 (published U.S. application No. US-2002-0128545-A1) entitled “Method of Measuring Transcutaneous Access Blood Flow,” filed [on even date herewith,] Dec.29, 2000, which is incorporated herein in its entirety.

The accuracy of the measurements taken using the TQ_(a) sensor 12 depends critically on at least two factors. As can be seen in equation (3) above, the calculated access flow rate depends directly on the volume of saline injected; therefore, care must be taken to inject a given amount of saline over a specified time interval. The latter does not need to be known precisely; however, it is important that it be less than approximately 10 seconds to avoid significant interference due to cardiopulmonary recirculation (CPR) of the injected saline. The second factor that is important to consider in the accuracy of the TQ_(a) measurements is the placement of the TQ_(a) sensor 12 to accurately determine changes in hematocrit through the skin. The sensor 12 must be placed directly over the vascular access site 14 approximately 25 mm downstream of the venous needle 24 in the specified orientation to accurately determine the relative changes in hematocrit. Additional variability due to sensor placement does not appear, however, to be significant, in that small variations in sensor placement do not significantly influence the measured vascular access flow rate. An additional concern is whether variations in accuracy of measurements taken using the TQ_(a) sensor 12 may occur with access sites that are not superficial or if the access diameter is very large; however, varying the spacing of sensor elements eliminates difficulties associated with very large accesses or with deeper access sites such as those typically found in the upper arm or thigh. Less accurate results would also be obtained if the sensor 12 does not accurately detect changes in hematocrit due to significant variation in skin pigmentation. The TQ_(a) sensor in accordance with the invention has been specifically designed to account for the individual absorption and scattering properties of patient tissues, through the use of 805 nm-880 nm LED optical technology, and the normalized nature of the measurements $\left( \frac{di}{i} \right)$ suggests that the sensitivity of the calculated vascular access flow rate to skin melanin content is minimal.

Referring now to FIGS. 2-6, there is shown a first embodiment of the TQ_(a) sensor 100 in accordance with the present invention for the transcutaneous measurement of vascular access blood flow in a hemodialysis shunt or fistula 14. In this embodiment two emitters 102 a and 102 b and two detectors 104 a and 104 b are arranged in alignment along an axis A1 on a substrate 110. As mentioned above, this embodiment is employed if a gradient in α_(o) exists in the area of interest (as is often the case in vivo), as multiple measurements must be made to establish the nature of the gradient and provide an averaged estimate of α_(o).

The sensor 100 has an access placement line L1 perpendicular to the axis A1. For proper operation, the sensor 100 must be placed with the access placement line L1 over the venous access site (shunt) 14. One of the emitters (the “inboard emitter”) 102 a and one of the detectors (the “inboard detector”) 104 a are placed at inboard positions on either side of and equidistant from the access placement line L1. The second emitter (the “outboard emitter”) 102 b is placed at a position outboard of the inboard detector 104 a, while the second detector (the “outboard detector”) 104 b is placed at a position outboard of the inboard emitter 102 a, so that the emitters 102 a and 102 b and detectors 104 a and 104 b alternate. The spacing between the emitters 102 a and 102 b and the detectors 104 a and 104 b is uniform.

The substrate 110 is provided with apertures 116 in its lower surface (the surface which in use faces the access site 20) for receiving the emitters 102 a and 102 b and the detectors 104 a and 104 b. The apertures 116 are sized so that the emitters 102 a and 102 b and the detectors 104 a and 104 b lie flush with the lower surface of the substrate 110.

Preferably, the upper surface of the substrate 110 is marked with the access placement line L1. The upper surface of the substrate 110 may also be provided with small projections 120 or other markings above the apertures 116 indicating the locations of the emitters 102 a and 102 b and the detectors 104 a and 104 b.

The circuitry (not shown) associated with the emitters 102 a and 102 b and the detectors 104 a and 104 b can be provided as a printed circuit on the lower surface of the substrate 110. The substrate 110 is made of a material that is flexible enough to conform to the contours of the underlying tissue but rigid enough to have body durability.

As shown in FIG. 7, there are three illuminated volumes or “glowballs” 130 a, 130 b, and 130 c in the tissue, T, seen by the two detectors 104 a and 104 b: a first glowball 130 a representing the reflective penetration volume (α) of the inboard emitter 102 a through the access site tissue as seen by the inboard detector 104 a in the process of determination of the access Hematocrit; a second glowball 130 b representing the reflective penetration (α_(o1)) of the inboard emitter 102 a through the non-access site tissue that surrounds the access site 14 as seen by the outboard detector 104 b; and a third glowball 130 c representing the reflective penetration (α_(o2)) of the outboard emitter 102 b through the non-access site tissue that surrounds the access site 14 as seen by the inboard detector 104 a. An estimate of α_(o) is made by averaging α_(o1) and α_(o2). That is, $\begin{matrix} {\alpha_{o} = \frac{\alpha_{o1} + \alpha_{o2}}{2}} & (14) \end{matrix}$

Due to the depth of the access site 14, in order for the cross-section of the access site 14 to be enclosed by the glowball 130 a of the inboard emitter 102 a seen by the inboard detector 104 a, the spacing between the inboard emitter 102 a and the inboard detector 104 a is typically 24 mm.

Referring now to FIGS. 8-12, there is shown a second embodiment of the TQ_(a) sensor 200 in accordance with the present invention. In this embodiment two emitters 202 a and 202 b and one detector 204 are arranged in alignment along an axis A2 on a substrate 210. As mentioned above, this embodiment is employed if the tissue, T, is more or less homogenous, and it is only necessary to make a single reference α_(o) measurement.

The sensor 200 has an access placement line L2 perpendicular to the axis A2. One of the emitters (the “inboard emitter”) 202 a and the detector 204 are placed at inboard positions on either side of and equidistant from the access placement line L2. The second emitter (the “outboard emitter”) 202 b is placed at a position outboard of the detector 204, so that the emitters 202 a and 202 b and the detector 204 alternate. The spacing between the emitters 202 a and 202 b and the detector 204 is uniform.

The substrate 210 is provided with apertures 216 in its lower surface for receiving the emitters 202 a and 202 b and the detector 204. The apertures 216 are sized so that the emitters 202 a and 202 b and the detector 204 lie flush with the lower surface of the substrate 210.

Preferably, the upper surface of the substrate 210 is marked with the access placement line L2, and also is marked with “plus” and “minus” signs 218 a and 218 b, which indicate the direction to move the sensor 200 left or right. The upper surface of the substrate 210 may also be provided with small projections 220 or other markings above the apertures 216 indicating the locations of the emitters 202 a and 202 b and the detector 204.

The circuitry (not shown) associated with the emitters 202 a and 202 b and the detector 204 can be provided as a printed circuit on the lower surface of the substrate 210. The substrate 210 is made of a material that is flexible enough to conform to the contours of the underlying tissue but rigid enough to have body durability.

As shown in FIG. 13, there are two illuminated “glowballs” 230 a and 230 b seen by the single detector 204: a first glowball 230 a representing the reflective penetration (α) of the inboard emitter 202 a through the access site tissue as seen by the single detector 204 in the process of determination of the access Hematocrit; and a second glowball 230 b representing the reflective penetration (α_(o)) of the outboard emitter 202 b through the non-access site tissue that surrounds the access site 14 as seen by the single detector 204.

Referring now to FIGS. 14-18, there is shown a third embodiment of the TQ_(a) sensor 300 in accordance with the present invention. The third embodiment is similar to the second embodiment, except that one emitter 302 and two detector 304 a and 304 b are arranged in alignment along an axis A3 on a substrate 310.

The sensor 300 has an access placement line L3 perpendicular to the axis A3. The emitter 302 and one of the detectors (the “inboard detector”) 304 a are placed at inboard positions on either side of and equidistant from the access placement line L3. The second detector (the “outboard detector”) 304 b is placed at a position outboard of the emitter 302, so that the emitter 302 and the detectors 304 a and 304 b alternate. The spacing between the emitter 302 and the detectors 304 a and 304 b is uniform.

The substrate 310 is provided with apertures 316 in its lower surface for receiving the emitter 302 and the detectors 3204 a and 3204 b. The apertures 316 are sized so that the emitter 302 and the detectors 304 a and 304 b lie flush with the lower surface of the substrate 210.

The circuitry (not shown) associated with the emitter 302 and the detectors 304 a and 304 b can be provided as a printed circuit on the lower surface of the substrate 310. The substrate 310 is made of a material that is flexible enough to conform to the contours of the underlying tissue but rigid enough to have body durability.

Preferably, the upper surface of the substrate 310 is marked with the access placement line L3, and also is marked with “plus” and “minus” signs 318 a and 318 b, which indicate the direction to move the sensor 300 left or right. The upper surface of the substrate 310 may also be provided with small projections 320 or other markings above the apertures 316 indicating the locations of the emitter 302 and the detectors 304 a and 304 b.

As shown in FIG. 19, there are two illuminated “glowballs” 330 a and 330 b seen by the detectors 304 a and 304 b: a first glowball 330 a representing the reflective penetration (α) of the single emitter 302 through the access tissue as seen by the inboard detector 304 a in the process of determination of the access Hematocrit; and a second glowball 330 b representing the reflective penetration (α_(o)) of the single emitter 302 through the non-access site tissue that surrounds the access site 14 as seen by the outboard detector 304 b

In the first three embodiments, the placement of the emitters and detectors permits all of the measurements to be made only in tissue volumes perpendicular to the access site 14. There will now be discussed fourth and fifth embodiments, in which the placement of the emitters and detectors permits measurements to be made in tissue areas parallel, as well as perpendicular, to the access site 14.

Referring to FIGS. 20-22, there is shown a fourth embodiment of the TQ_(a) sensor 400 in accordance with the present invention. In the fourth embodiment, a flexible components layer 410 is provided having an access placement line L4. An upstream and a downstream emitter 402 a and 402 b are arranged on the components layer 410 along a first diagonal line D1 forming a 45° angle with the access placement line L4, and an upstream and a downstream detector 404 a and 404 b are arranged along a second line D2 perpendicular to the first line at its point of intersection P with the access placement line L4. The upstream and downstream emitters 402 a and 402 b and the upstream and downstream detectors 404 a and 404 b are equidistant from the point of intersection P. It will thus be seen that the upstream emitter 402 a and the downstream detector 404 b lie on one side of the access placement line L4 along a line parallel thereto, and the upstream detector 404 a and the downstream emitter 402 b lie on the other side of the access placement line LA along a line parallel thereto; and that the upstream emitter 402 a and the upstream detector 404 a lie along a line perpendicular to the access placement line L4, as do the downstream emitter 402 b and the downstream detector 404 b.

In the TQ_(a) sensor 400 in accordance with the fourth embodiment, the circuitry associated with the emitters 402 a and 402 b and the detectors 404 a and 404 b is also incorporated in the flexible components layer 410. The components layer 410 has a lower surface that faces the access site 14, and an upper surface that faces away. The emitters 402 a and 402 b and the detectors 404 a and 404 b may protrude from the lower surface of the components layer 410. A cover layer 412 of flexible foam or the like covers the upper surface of the components layer 410. A spacer layer 414 of flexible foam or the like covers the lower surface of the components layer 410, and has apertures 416 in registration with the emitters 402 a and 402 b and the detectors 404 a and 404 b, so that each emitter and detector is received in its own corresponding aperture 416. The spacer layer 414 has an upper surface that contacts the lower surface of the components layer 410 and a lower surface that faces away from the components layer 410.

Preferably, the upper surface of the cover layer 412 is marked with the access placement line L4, and also is marked to indicate which end of the access placement line L4 is to be placed adjacent the venous needle 24, to assist in proper placement. Also, the TQ_(a) sensor 400 preferably is elongated in the direction of the access placement line L4, in order to ensure the proper placement of the emitters 402 a and 402 b and the detectors 404 a and 404 b relative to the venous needle 24.

In order to hold the TQ_(a) sensor 400 in place, a transparent adhesive layer 420 can be applied to the lower surface of the spacer layer 414. The adhesive can be any suitable pressure sensitive adhesive. A release liner 422 covers the adhesive layer 420. Prior to use, the release layer 424 is removed from the adhesive layer 420 of the TQ_(a) sensor 400, and the TQ_(a) sensor 400 is adhered to the access site 14.

As shown in FIGS. 23-26, there are four illuminated “glowballs” seen by the upstream and downstream detectors: a first glowball 430 a representing the reflective penetration (α) of the upstream emitter 402 a through the access site tissue as seen by the upstream detector 404 a in the process of determination of the access hematocrit (FIG. 23); a second glowball 430 b representing the reflective penetration (α) of the downstream emitter 402 b through the access site tissue as seen by the downstream detector 404 b in the process of determination of the access Hematocrit (FIG. 24); a third glowball 430 c representing the reflective penetration (α_(o1)) of the upstream emitter 402 a through the non-access site tissue that surrounds the access site 14 as seen by the downstream detector 404 b (FIG. 25); and a fourth glowball 430 d representing the reflective penetration (α_(o2)) of the downstream emitter 404 b through the non-access site tissue that surrounds the access site 14 as seen by the upstream detector 404 a (FIG. 26). An estimate of α_(o) is again made by averaging α_(o1) and α_(o2).

Referring to FIGS. 27-29, there is shown a fifth embodiment of the TQ_(a) sensor 500 in accordance with the present invention. In the fifth embodiment, a substrate 510 is provided having an access placement line L5. A first upstream emitter 502 a and a downstream emitter 502 b are arranged on the substrate 510 along a first diagonal line D3 forming a 45° angle with the access placement line L5, and upstream and downstream detectors 504 a and 504 b are arranged along a second line D4 perpendicular to the first line at its point of intersection P with the access placement line L4, exactly as in the fourth embodiment, with the first upstream and the downstream emitters 502 a and 502 b and the upstream and downstream detectors 504 a and 504 b being equidistant from the point of intersection P. In addition, the second, third, fourth, fifth, and sixth upstream detectors 502 c, 502 d, 502 e, 502 f, and 502 g are arranged in alignment along a line defined by the first upstream emitter 502 a and the upstream detector 504 a, with the fourth detector 502 e lying on the access placement line L5. The second, third, fourth, fifth, and sixth emitters 502 c, 502 d, 502 e, 502 f, and 502 g are uniformly spaced between the first upstream emitter 502 a and the upstream detector 504 a and can be used to locate the access. In addition, pairs of emitters 502 a and 502 c-502 g can be used to determine the diameter of the access.

The cover layer 512, spacer layer 514, adhesive layer 522, and release liner 524 of the sensor 500 in accordance with the fifth embodiment are identical to those of the sensor 400 of the fourth embodiment, except that the apertures 516 in the spacer layer 514 will be placed in accordance with the placement of the emitters 502 a-502 g and the detectors 504 a and 504 b in the components layer 510 of the fifth embodiment.

As shown in FIGS. 30 and 31, there are six illuminated glowballs perpendicular to the access site 14 and one illuminated glowball parallel to the access site 14 that are seen by the upstream detector 504 a: a first glowball 530 a representing the reflective penetration (α) of the first upstream emitter 502 a through the access site tissue in the process of determination of the access site Hematocrit (FIG. 30); a second glowball 530 b representing the reflective penetration (α_(o1)) of the downstream emitter 502 b through the non-access site tissue that is parallel to the access site 14 (FIG. 31); a third glowball 530 c representing the reflective penetration of the second upstream emitter 502 c through both non-access and some of the access volume (FIG. 30); a fourth glowball 530 d representing the reflective penetration of the third upstream emitter 502 d through both non-access and some of the access volume (FIG. 30); a fifth glowball 530 e representing the reflective penetration of the fourth upstream emitter 502 e through both non-access and some of the access volume (FIG. 30); a sixth glowball 530 f representing the reflective penetration of the fifth upstream emitter 502 f through non-access the access volume (FIG. 30); and a seventh glowball 530 g representing the reflective penetration of the sixth upstream emitter 502 g through non-access volume (FIG. 30).

As shown in FIGS. 32 and 33, there are two illuminated “glowballs” seen by the downstream detector 504 b: an eighth glowball 530 h representing the reflective penetration (α_(o2)) of the first upstream emitter 502 a through the non-access site tissue that is parallel to the access site 14 (FIG. 32); and a second glowball 530 i representing the reflective penetration (α) of the downstream emitter 502 b through the access site tissue in the process of determination of the access Hematocrit (FIG. 33). An estimate of α_(o) is made by averaging α_(o1) and α_(o2), and then using equation (13) to determine ${F\left( \frac{\Delta\quad H}{H} \right)}.$

Due to the depth of the access site 14, in order for the cross-section of the access site 14 to be enclosed by the glowball of the first upstream emitter 502 a seen by the upstream detector 504 a, the spacing between the first upstream emitter 502 a and the upstream detector 504 a is typically 24 mm. The remaining upstream emitters 502 c-502 g are equally spaced between the first upstream emitter 502 a and the upstream detector 504 a. Similarly, the spacing between the downstream emitter 502 b and the downstream detector 504 b are typically 24 mm.

As indicated above, in all of the embodiments, the emitters are preferably LEDs that emit light at a wavelength of 805 nm-880 nm, and the detectors are silicon photodiodes. In the first three embodiments shown in FIGS. 2-6, 8-12, and 14-18, the substrate preferably is provided with an exterior covering (see FIG. 34) of a plastic material, for example urethane or silicone, and the emitters and detectors lie flush with the lower surface of the exterior covering, that is, the surface that faces the skin, so that the emitters and detectors lie on the skin. In the fourth and fifth embodiments shown in FIGS. 20-22 and 27-29, each emitter and detector is recessed in an aperture. The fourth and fifth embodiments use more LED's than the other embodiments.

Also in all of the embodiments, an emitter-detector separation is required so that the reflectance of the first layer of tissue (a non-blood layer of epithelium) does not further exaggerate a multiple scattering effect, as discussed in U.S. Pat. No. 5,499,627, which is incorporated herein by reference in its entirety.

Further, in the all of the embodiments, the distance between each adjacent pair of emitters and detectors must be sufficient for a portion of the access site 14 to be enclosed within the illuminated volume or “glowball” of the inboard emitter. This distance typically is about 24 mm, except as described above with respect to the fifth embodiment.

Finally, in all of the embodiments, the sensor can be fastened in place using surgical tape. Alternatively, any of the embodiments can be made as a disposable adhesive patch that cannot be recalibrated and used again. Referring to FIG. 34, a sensor 600 includes a substrate 610 that houses a plurality of emitters and detectors (not shown) as previously described, a circuit 652 printed on the skin side of the substrate 610, and an exterior covering 654 covering the circuit 652 and the exposed sides of the substrate 610. The substrate 610 can comprise a flexible material such as MYLAR on which conductive paint has been deposited to define a circuit. Apertures 656 are formed through the skin side of the exterior covering 654 in registration with circuit junctions that are covered by conductive paint that allows continuity across the junctions. Plugs 660 are inserted into the apertures 656 in such a fashion that they adhere to the conductive paint at the circuit junctions. The skin side of the exterior covering 654 is covered by a removable protective layer 662, to which the plugs 660 are also affixed.

Following removal of the sensor 600 from its sterile package and pre-use test and calibration, the protective surface protective layer 662 must be removed in order for the sensor 600 to take a measurement. Because the plugs 660 are adhered to the protective layer 662, when the protective layer 662 is peeled off, the plugs 660 are pulled out of their apertures 656 along with the conductive paint covering the circuit junctions. The circuitry is designed such that once the circuit is broken, the sensor 600 cannot be calibrated again, and can only be used to take one measurement. The sensor 600 thus cannot be re-used.

Operability of the TQ_(a) sensor in accordance with the invention was confirmed in in vivo tests in 59 hemodialysis patients. Prior to the study dialysis session, a disposable tubing with an injection port (CO-daptoR, Transonic Systems, Ithaca, N.Y., USA) was placed between the venous dialysis tubing and the venous needle. The dialysis circuit was primed with saline in usual fashion taking extra care to remove any air bubbles from the venous injection port.

Within the first hour of dialysis, access recirculation was first measured by the HD01 monitor (Transonic Systems). Then, the dialyzer blood pump was stopped, the dialysis lines were reversed from their normal configuration, and the access blood flow rate was determined, in duplicate, by the HD01 monitor (Transonic Systems). Injection of saline was performed using the saline release method (abstract: Krivitski et al, J Am Soc Nephrol 8:164A, 1997). The dialyzer blood pump was again stopped and the dialysis lines were returned to their normal configuration.

After the dialysis blood lines were returned to the normal configuration and the dialyzer blood pump was restarted, the transcutaneous hematocrit sensor was placed on the skin over the patient's vascular access approximately 25 mm downstream of the venous needle. Thirty ml of normal saline solution were then injected into the injection port of the disposable tubing adjacent to the venous needle at a rate of approximately 300 nm/min to determine access blood flow rate using the TQ_(a) sensor of the invention. In six patients, saline was injected directly into the arterial dialysis needle before connecting the needle to the complete dialysis circuit. In two patients, saline was injected directly into the access by using a needle and syringe. The data from these various methods were combined together, independent of where saline was injected into the access. The resulting $F\left( \frac{\Delta\quad H}{H} \right)$ signal proportional to $\frac{\Delta\quad H}{H}$ is shown in FIG. 35 with the saline bolus. In 38 patients, this measurement was performed in duplicate to assess the replicability of the method.

All measured and calculated values are reported as mean±SD. The significance of differences in calculated vascular access flow rates determined using the TQ_(a) sensor and those determined by the HD01 monitor was determined using a paired Student's t-test. The variability of the slope and intercept from the regression equation is expressed as± the estimated SD (or the SE). The results from the replicability and reproducibility studies are expressed as the average coefficient of variation for the duplicate measurements. P values less than 0.05 were considered statistically significant.

The patients studied were predominantly male and Caucasian; 5 Black and 1 Native American patients were studied. Although the distribution of patient race in the study was not representative of that within the United States as a whole, it was representative of the population in the geographical region where the test was conducted. The age of the patients, the fraction of diabetic patients and the fraction of patients with synthetic PTFE grafts were similar to those for chronic hemodialysis patients in the United States. Eleven patients were studied twice and one patient was studied three times. All other patients were studied once for a total of 72 measurements. Access recirculation was significant in three patients. In those patients, the blood pump setting was reduced to 150 ml/min to eliminate access recirculation before completing the study protocol.

FIG. 36 shows values of the vascular access flow rate determined using the TQ_(a) sensor plotted versus that determined by the HD01 monitor. The best-fit linear regression line has a slope of essentially unity and a small y-intercept. There was no significant difference between vascular access flow rates determined using the TQ_(a) sensor and those determined by the HD01 monitor; the mean absolute difference between these methods was 71±63 ml/min. When these results were analyzed for various patient subgroups (male vs. female, black vs. white, diabetic vs. nondiabetic, synthetic grafts vs. native fistulas), excellent agreement between the measured access blood flow rates was similarly observed.

Because the optical TQ_(a) sensor in accordance with the invention can accurately determine instantaneous changes in hematocrit, it permits use of the bolus injection indicator dilution approach (Henriques-Hamilton-Bergner Principle). This optical approach is likely to be of considerable interest to nephrologists since it is also possible to determine the vascular access flow rate when the patient is in the physician's office or in the clinic and not being treated by hemodialysis by simply injecting saline directly into the access and measuring with a downstream TQ_(a) sensor. During the initial study, eight patients had vascular access flow rate determinations by direct injection of saline into the access prior to dialysis; their results were later confirmed once the dialysis circuit was in place and functioning. Furthermore, two additional studies were perfored excusively by injecting saline into the access, with excellent results. Thus, it may now be possible to use the TQ_(a) sensor in accordance with the invention to regularly monitor the vascular access flow rate as an indicator of access function when the patient is not being dialyzed, as well as during maturation of native fistulas prior to first use.

Modifications and variations of the above-described embodiments of the present invention are possible, as appreciated by those skilled in the art in light of the above teachings. For example, the sensor in accordance with the present invention can be used to measure blood constituents other than hematocrit, such as albumen and glucose, in which case the LEDs emit different wavelengths suited to the specific constituent.

Further, the detector-emitter arrangement of the sensor in accordance with the present invention, and in particular of the sensor 110 shown in FIG. 7, allows for precise access location, as a “flow finder,” and also can be used to locate grafts and to localize veins in normal patients for more efficient canulatization. In this connection, the sensor 110 is placed directly on the skin over the approximate area of the access, graft, or vein, and values of α, α₁, and α₂ are calculated as described above. A reference ratio, RR, is developed, where: ${RR} = {\left( {1 - \frac{\alpha_{o1}}{\alpha_{02}}} \right) \times 100}$ When RR<±15, then the access or graft or vein is “centered” correctly or found between the inboard LED 102 a and the inboard detector 104 a. Also, a signal strength (SS) indicator advises the user whether a sufficient signal is present for an accurate measurement, where ${SS} = \left\lbrack {\left( {\alpha - \left( \frac{\alpha_{o1} + \alpha_{o2}}{2} \right)} \right\rbrack \times 100} \right.$ When SS>40, then a sufficient amount of the access or graft or vein is within the illuminated volume of tissue. If RR is not<+15 (that is, if RR≧±15), or if SS is not>40 (that is, if SS is<40), then the sensor 110 is moved right or left (+ or −) to find the appropriate spot or location.

It is therefore to be understood that, within the scope of the appended claims and their equivalents, the invention may be practiced otherwise than as specifically described. 

1. A medical device to be secured to the skin of a patient to measure a physical parameter comprising: a substrate having a skin surface and an exterior surface; a flexible circuit board mounted on the exterior surface; conductive paint deposited on the circuit board to define a circuit that operates to allow calibration of the medical device when the circuit is complete and prevents calibration of the medical device when a portion of the conductive paint is removed from the circuit board; an aperture formed through the substrate to provide a passage from the skin surface to the conductive path; a plug positioned within the aperture to adhere to the conductive paint; and a removable protective layer covering the skin surface of the substrate and secured to the plug so that when the protective layer is removed the plug remains secured to the protective layer resulting in removal of a portion of the conductive paint to prevent calibration of the medical device.
 2. The medical device of claim 1, further comprising an exterior cover positioned on the exterior surface of the substrate to define an interior portion of the substrate; and a plurality of sensing elements housed in the interior portion of the substrate and secured to the circuit board. 